BACKGROUND & AIMS: Improved therapeutic options for chronic hepatitis C virus (HCV) infection are needed for patients who are poor candidates for treatment with current regimens due to anticipated intolerability or low likelihood of response. METHODS: In this open-label, phase 2a study of Japanese patients with chronic HCV genotype 1b infection, 21 null responders (<2 log₁₀ HCV RNA reduction after 12 weeks of peginterferon/ribavirin) and 22 patients intolerant to or medically ineligible for peginterferon/ribavirin therapy received dual oral treatment for 24 weeks with the NS5A replication complex inhibitor daclatasvir (DCV) and the NS3 protease inhibitor asunaprevir (ASV). The primary efficacy end point was sustained virologic response at 12 weeks post-treatment (SVR₁₂). RESULTS: Thirty-six of 43 enrolled patients completed 24 weeks of therapy. Serum HCV RNA levels declined rapidly, becoming undetectable in all patients on therapy by week 8. Overall, 76.7% of patients achieved SVR₁₂ and SVR₂₄, including 90.5% of null responders and 63.6% of ineligible/intolerant patients. There were no virologic failures among null responders. Three ineligible/intolerant patients experienced viral breakthrough and four relapsed post-treatment. Diarrhea, nasopharyngitis, headache, and ALT/AST increases, generally mild, were the most common adverse events; three discontinuations before week 24 were due to adverse events that included hyperbilirubinemia and transaminase elevations (two patients). CONCLUSIONS: Dual therapy with daclatasvir and asunaprevir, without peginterferon/ribavirin, was well tolerated and achieved high SVR rates in two groups of difficult-to-treat patients with hepatitis C virus genotype 1b infection.
BACKGROUND & AIMS: Improved therapeutic options for chronic hepatitis C virus (HCV) infection are needed for patients who are poor candidates for treatment with current regimens due to anticipated intolerability or low likelihood of response. METHODS: In this open-label, phase 2a study of Japanese patients with chronic HCV genotype 1b infection, 21 null responders (<2 log₁₀ HCV RNA reduction after 12 weeks of peginterferon/ribavirin) and 22 patients intolerant to or medically ineligible for peginterferon/ribavirin therapy received dual oral treatment for 24 weeks with the NS5A replication complex inhibitor daclatasvir (DCV) and the NS3 protease inhibitor asunaprevir (ASV). The primary efficacy end point was sustained virologic response at 12 weeks post-treatment (SVR₁₂). RESULTS: Thirty-six of 43 enrolled patients completed 24 weeks of therapy. Serum HCV RNA levels declined rapidly, becoming undetectable in all patients on therapy by week 8. Overall, 76.7% of patients achieved SVR₁₂ and SVR₂₄, including 90.5% of null responders and 63.6% of ineligible/intolerant patients. There were no virologic failures among null responders. Three ineligible/intolerant patients experienced viral breakthrough and four relapsed post-treatment. Diarrhea, nasopharyngitis, headache, and ALT/AST increases, generally mild, were the most common adverse events; three discontinuations before week 24 were due to adverse events that included hyperbilirubinemia and transaminase elevations (two patients). CONCLUSIONS: Dual therapy with daclatasvir and asunaprevir, without peginterferon/ribavirin, was well tolerated and achieved high SVR rates in two groups of difficult-to-treat patients with hepatitis C virus genotype 1b infection.